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1.
Keiko Goto Yutaka Fujiwara Takeshi Isobe Naoko Chayahara Naomi Kiyota Toru Mukohara Yukari Tsubata Takamasa Hotta Kenji Tamura Noboru Yamamoto Hironobu Minami 《Cancer science》2019,110(6):1987-1994
Although dose reduction of S‐1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5‐fluorouracil, 5‐chloro‐2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S‐1 in patients with renal impairment. We classified patients receiving S‐1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S‐1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m2), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m2), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m2), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m2). Those in cohorts 3 and 4 treated with an adjusted dose of S‐1 showed a similar area under the curve for 5‐fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S‐1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S‐1 in patients with impaired renal function using eGFR is appropriate and safe. 相似文献
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Daisuke Ishii Daisuke Matsuzawa Shingo Matsuda Haruna Tomizawa-Shinohara Chihiro Sutoh Eiji Shimizu 《The International journal of neuroscience》2019,129(1):1-9
Adolescence is a vulnerable period for developing anxiety-related mental disorders such as post-traumatic stress disorder (PTSD), which requires a long-term course of therapy when a traumatic event has been experienced during childhood. However, the biological mechanism underlying these age-dependent characteristics remains unclear. In the present study, we used early adolescent, late adolescent and adult (4-, 8-, and 15-week old) male mice to examine age differences in fear memory, fear extinction, and spontaneous recovery of fear. We also measured the activation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus (dHip) and the basolateral amygdala (BLA) following a spontaneous recovery test. Our major findings were as follows: (1) early adolescent and adult mice did not recover the fear response; only late adolescent mice recovered the fear response. (2) The ERK2 in the dHip was more activated after the spontaneous recovery test in late adolescent mice than in adult mice, and the ERK2 in the BLA was more activated after the spontaneous recovery test in adult mice than in late adolescent mice. These results suggest that there exists a unique period in which spontaneous recovery occurs and that these late adolescent behavioral signatures may be related to alteration in the ERK2 phosphorylation in the dHip and BLA. 相似文献
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Eitaro Ito Akihiro Takai Yoshinori Imai Hiromi Otani Yoshihiro Onishi Yosuke Yamamoto Kohei Ogawa Taiji Tohyama Shunichi Fukuhara Yasutsugu Takada 《Surgery》2019,165(2):353-359
Background
Controversy continues as to whether single-incision laparoscopic cholecystectomy, with the somewhat larger incision at the umbilicus, may lead to a worse postoperative quality of life and more pain compared with the more classic 4-port laparoscopic cholecystectomy. The aim of this study was to compare single-incision and 4-port laparoscopic cholecystectomy from the perspective of quality of life.Methods
This study was a multicenter, parallel-group, open-label, randomized clinical trial. A total of 120 patients who were scheduled to undergo elective cholecystectomy were randomly assigned 1:1 into the single-incision laparoscopic cholecystectomy or the 4-port laparoscopic cholecystectomy group and then assessed continuously for 2 weeks during the postoperative period. The primary outcome was quality of life, defined as the time to resume normal daily activities. Postoperative pain was also assessed. To explore the heterogeneity of treatment effects, we assessed the interactions of sex, age, and working status on recovery time.Results
A total of 58 patients in the single-incision group and 53 in the 4-port group (n?=?111, 47 male, mean age 57 years) were analyzed. The mean time to resume daily activities was 10.2 days and 8.8 days, respectively, for single-incision and 4-port laparoscopic cholecystectomy (95% confidence interval –0.4 to 3.2, P?=?.12). Similarly, the time to relief from postoperative pain did not differ significantly between the groups. Statistically insignificant but qualitative interactions were noted; in the subgroups of women, full-time workers, and patients younger than 60 years, recovery tended to be slower after single-incision laparoscopic cholecystectomy.Conclusion
Postoperative quality of life did not differ substantially between single-incision laparoscopic cholecystectomy and 4-port laparoscopic cholecystectomy. Patients younger than 60 years, women, and full-time workers tended to have a somewhat slower recovery after single-incision laparoscopic cholecystectomy. 相似文献7.
Dermoscopic features of hidroacanthoma simplex: Usefulness in distinguishing it from Bowen's disease and seborrheic keratosis 下载免费PDF全文
Chihiro Shiiya Hiroo Hata Yuka Inamura Keisuke Imafuku Shinya Kitamura Hiromi Fujita Hiroshi Shimizu 《The Journal of dermatology》2015,42(10):1002-1005
Hidroacanthoma simplex (HAS) is a rare benign eccrine adnexal tumor. HAS is sometimes clinically or pathologically misdiagnosed as squamous cell carcinoma in situ (Bowen's disease; BD), seborrheic keratosis (SK) or other adnexal tumor. To date, there has never been a report focusing on dermoscopic features to distinguish HAS from BD and SK. We found the following dermoscopic findings to be characteristic of HAS: fine black dots/globules (75% of cases) and fine scales arranged annularly (100% of cases). In contrast, glomerular vessels, which are typically observed in BD, were not seen in any of the four cases. Cerebriform appearance and milia‐like cysts, which are typically observed in SK, were also not seen in any of the four cases. The existence of “scattered fine black dots/globules” and “fine scales arranged annularly”, and the absence of the glomerular vessels, may contribute to precise diagnosis of HAS. Even though HAS resembles BD or SK clinically, it can be distinguished from these by the characteristic dermoscopic features. 相似文献
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Takaharu Negoro Kanami Orihara Tomoko Irahara Hiroshi Nishiyama Kanae Hagiwara Risa Nishida Hiroki Takagi Kazue Satoh Yoshiki Yamamoto Shunichi Shimizu Tamio Hagiwara Masakazu Ishii Toshihiro Tanioka Yasuko Nakano Ken Takeda Isao Yoshimura Yoji Iikura Takashi Tobe 《Pediatric allergy and immunology》2006,17(8):583-590
Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity. 相似文献
10.
Kei Kamide Yoshihiro Kokubo Hironori Hanada Junko Nagura Jin Yang Shin Takiuchi Chihiro Tanaka Mariko Banno Yoshikazu Miwa Masayoshi Yoshii Tetsutaro Matayoshi Hisayo Yasuda Takeshi Horio Akira Okayama Hitonobu Tomoike Yuhei Kawano Toshiyuki Miyata 《Hypertension research》2006,29(4):243-252
Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese. 相似文献